Akt and SHIP modulate Francisella escape from the phagosome and induction of the Fas-mediated death pathway.

PloS One
Murugesan V S RajaramSusheela Tridandapani

Abstract

Francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. Here we show that the Fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the bacterial burden. Our studies also demonstrate that constitutive activation of Akt, or deletion of SHIP, promotes phago-lysosomal fusion and limits bacterial burden in the host cytosol, and the subsequent induction of Fas expression and cell death. Finally, we show that phagosomal escape/intracellular bacterial burden regulate activation of the transcription factors sp1/sp3, leading to Fas expression and cell death. These data identify for the first time host cell signaling pathways that regulate the phagosomal escape of Francisella, leading to the induction of Fas and subsequent host cell death.

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Citations

Jun 13, 2012·Microbiology and Molecular Biology Reviews : MMBR·Crystal L JonesDavid S Weiss
Jun 23, 2010·Journal of Leukocyte Biology·Manuel T Silva
Sep 14, 2016·Journal of the American Heart Association·Michael A MakaraMurugesan V S Rajaram
Nov 7, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jason M ZimmererGinny L Bumgardner
Mar 30, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nrusingh P MohapatraJohn S Gunn
Jun 24, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thomas J CremerSusheela Tridandapani
Apr 1, 2017·Frontiers in Immunology·Daniel A Powell, Jeffrey A Frelinger
Jul 25, 2019·Frontiers in Cellular and Infection Microbiology·Klara Kubelkova, Ales Macela
Sep 27, 2019·Frontiers in Immunology·Taojing RanLiwu Li

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Methods Mentioned

BETA
transgenic
Flow Cytometry
protein assay
immunoprecipitation
Assay
confocal microscopy
immunoprecipitations

Software Mentioned

R
BioConductor
âlimmaâ
CellQuest
âgcrmaâ
Scion Image

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